Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a breakthrough treatment for relapsed and refractory multiple myeloma (RRMM). However, these products are complex to deliver, and alternative options are now available. Identifying biomarkers that can predict therapeutic outcomes is crucial for optimizing patient selection. There is a paucity of data evaluating the utility of both serum soluble B-cell maturation antigen (sBCMA) levels and metabolic tumor volume (MTV) at baseline in patients with RRMM undergoing CAR-T therapy. We identified a cohort of 183 patients with available serum to measure sBCMA and/or pretreatment MTV, derived from positron emission tomography–computed tomography scans obtained per standard of care. Expectedly, high pretreatment levels of sBCMA correlated with other established markers of tumor burden (eg, bone marrow plasma cells and β2 microglobulin) and inflammation and were highly prognostic for CAR-T–related toxicities and inferior progression-free survival (PFS). High MTV values were also associated with shorter PFS and inferior overall survival. The poor correlation observed between these 2 measures prompted evaluation of those with discordant results, identifying that those with low sBCMA and high MTV frequently had low/absent BCMA expression on plasma cells and suboptimal response. Our findings highlight the potential utility of sBCMA and MTV to facilitate more personalized treatment strategies in the management of RRMM eligible for BCMA-directed CAR-T.

Trastuzumab-deruxtecan (T-DXd) has demonstrated intracranial efficacy; however, safety and efficacy data remains limited with stereotactic radiosurgery (SRS). A multi-institutional review was performed with HER2+ or HER2-low metastatic breast cancer treated with T-DXd and SRS for active brain metastases. We identified 215 lesions treated over 48 SRS courses in 34 patients. Median follow up from T-DXd initiation was 13.9 months. The cumulative incidence of symptomatic radiation necrosis at 24 months per lesion was 2.1% and per patient 11%. The 12-month LC was 97%. HER2-low was associated with worse distant intracranial control (DIC) (adjusted HR 2.5, 95% CI 1.1–5.6, p = 0.03) and worse systemic progression free survival (PFS) (HR 4.1, 95% CI 1.6–10.7, p = 0.004). Concurrent SRS and T-DXd has excellent local control, without an increased risk of radiation necrosis. HER2-low disease is associated with worse systemic PFS and DIC with T-DXd compared to HER2+.

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. Methods: The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Results: Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. Conclusions: While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.